Clinical or real effectiveness of psychopharma is very rare via common pooping-out, many treatment-refractory patients and up to half of patients fail to attain remission (S. M. Stahl, Essential Psychopharmacology, 2000). Implications of not attaining remission for Mental Disorders are increased relapse rates, continuing functional impairment and increased suicide rate.
Clinical causes of not attaining remission by the Current Psychopharmacological Compounds are inadequate early treatment, underlying dysregulation of the emotional functionality (affect instability-hypersensitivity-hyperaesthesia-dissociative phenomena . . . ) and competitive antagonism.
Dysregulation of the HPA axis has frequently reported in patients with psychiatric disorders, and is among the most robustly demonstrated neurobiological changes among psychiatric patients (D. A. Gutman and C. B. Nemeroff, Biological Psychiatry, 2002). The resulting elevated plasma cortisol concentrations leads to an enhanced binding of serotonin for the 5-HT2A receptor (E. A. Young, Arch Gen Psychiatry/Vol 60, January 2003).
Results suggest that cortical D2 dopamine receptors are a common target of traditional and atypical antipsychotics for therapeutic action. Higher in vivo binding to the D2 receptors in the cortex than in the basal ganglia is suggested as an indicator of favourable profile for a putative antipsychotic compound (X. Xiberas and J. L. Martinot; The British Journal of Psychiatry (2001) 179: 503-508).
Data demonstrate that dopamine D4 receptors play an important role in the induction of behavioral sensitization to amphetamine and accompanying adaptations in pre- and postsynaptic neural systems associated with the mesolimbocortical dopamine projections (D. L. Feldpausch et al; The journal of pharmacology and experimental therapeutics Vol. 286, Issue 1, 497-508, July 1998). Further, results show that dopamine D4 receptor antagonism in the brain does not result in the same neurochemical consequences (increased dopamine metabolism or hyperprolactinemia) observed with typical neuroleptics (Smita Patel et al; The journal of pharmacology and experimental therapeutics Vol. 283, Issue 2, 636-647, 1997).
However, the selective D4 dopamine receptor antagonist L-745,870 was ineffective as an antipsychotic for the treatment of neuroleptic responsive inpatients with acute schizophrenia (Kramer M S et al; Arch Gen Psychiatry 1997 December; 54(12):1080.)
There is thus a growing need for a more efficient therapy and more efficient, selective and efficacious medicaments for treating mental disorders.